Combination of curcumin and vagus nerve stimulation attenuates cerebral ischemia/reperfusion injury-induced behavioral deficits

Abstract

AimPrevious studies indicated that cerebral ischemia/reperfusion injury (CI/RI) could induce behavioral deficits. Single treatment of vagus nerve stimulation (VNS) or curcumin is reported to restore CI/RI-induced behavioral deficits. However, the synergic effect remains unclear. Materials and methodsRats were divided into 6 groups: sham, CI/RI, VNS, CI/RI + VNS, VNS + curcumin and CI/RI + VNS + curcumin groups. Each group was further divided into three or four subgroups for further assessments. In specific, Morris water maze task and shuttle box test were used to evaluate cognitive capacity. Rota-rod test, neurological deficits scores, 2,3,5-triphenyltetrazolium chloride staining, TUNEL staining were performed to estimate motor capacity, neurological deficits, the size of infarct volume and neural apoptosis, respectively. Finally, the expressions of apoptosis-associated proteins and key kinases in the AKT/extracellular signal-regulated kinase-2 (ERK2) pathway were measured by Western blot analysis. ResultsCombination of curcumin and VNS significantly restored the CI/RI-induced cognitive and motor impairments compared with the CI/RI + VNS group (P < 0.05 and P < 0.01). Moreover, combination of curcumin and VNS significantly lowered CI/RI-induced neurological deficits, infract volume, neural apoptosis (all P < 0.05) and inflammatory cytokines release (P < 0.05 and P < 0.01) when compared to the CI/RI + VNS group. Additionally, the phosphorylation levels of AKT and ERK2 were both increased by combination of curcumin and VNS compared with the CI/RI + VNS group. ConclusionCombination of curcumin and VNS restored CI/RI-induced behavioral deficits by inhibiting apoptosis and inflammatory response. Besides, the AKT/ERK2 pathway might be implicated.